Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea

Kanamycin and cisplatin are ototoxic drugs. The mechanisms are incompletely known. With subcutaneous kanamycin (400 mg/kg, 15 days), auditory threshold shifts were detected at days 12–13 at 16 and 32 kHz, extending to 8 and 4 kHz at days 14–15. The outer hair cell (OHC) loss was concentrated past da...

Descripción completa

Detalles Bibliográficos
Autores: Gibaja, Alejandro, Alvarado Romero, Juan Carlos, Scheper, Verena, Carles, Liliana, Juiz Gómez, José Manuel
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/33175
Acceso en línea:https://doi.org/10.3390/antiox11091759
https://hdl.handle.net/10578/33175
Access Level:acceso abierto
Palabra clave:Antibiotic toxicity
Antioxidation
Auditory receptor
Cochlear toxicity
Deafness
id ES_fa244ace1bc6b616bdfdcba0dc5e64e9
oai_identifier_str oai:ruidera.uclm.es:10578/33175
network_acronym_str ES
network_name_str España
repository_id_str
spelling Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the CochleaGibaja, AlejandroAlvarado Romero, Juan CarlosScheper, VerenaCarles, LilianaJuiz Gómez, José ManuelAntibiotic toxicityAntioxidationAuditory receptorCochlear toxicityDeafnessKanamycin and cisplatin are ototoxic drugs. The mechanisms are incompletely known. With subcutaneous kanamycin (400 mg/kg, 15 days), auditory threshold shifts were detected at days 12–13 at 16 and 32 kHz, extending to 8 and 4 kHz at days 14–15. The outer hair cell (OHC) loss was concentrated past day 12. The maximum cochlear length showing apoptotic cells, tested with TUNEL, was at day 13. At day 15, 1/5 of the apical cochlea contained preserved OHCs. 3-nitrotyrosine (3-NT) immunolabeling, showing oxidative stress, was found in surviving OHCs and in basal and middle portions of the stria vascularis (SV). The antioxidant Gpx1 gene expression was decreased. The immunocytochemistry showed diminished Gpx1 in OHCs. With intraperitoneal cisplatin (16 mg/kg, single injection), no evoked auditory activity was recorded at the end of treatment, at 72 h. The basal third of the cochlea lacked OHCs. Apoptosis occupied the adjacent 1/3, and the apical third contained preserved OHCs. 3-NT immunolabeling was extensive in OHCs and the SV. Gpx1 and Sod1 gene expression was downregulated. Gpx1 immunostaining diminished in middle and basal SV. More OHCs survived cisplatin than kanamycin towards the apex, despite undetectable evoked activity. Differential regulation of antioxidant enzyme levels suggests differences in the antioxidant response for both drugs.MDPI202420242022info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://doi.org/10.3390/antiox11091759https://hdl.handle.net/10578/33175reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésSBPLY/17/180501/000544EXC 2177/1,ID: 390895286info:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/331752026-05-27T07:36:41Z
dc.title.none.fl_str_mv Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea
title Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea
spellingShingle Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea
Gibaja, Alejandro
Antibiotic toxicity
Antioxidation
Auditory receptor
Cochlear toxicity
Deafness
title_short Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea
title_full Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea
title_fullStr Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea
title_full_unstemmed Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea
title_sort Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea
dc.creator.none.fl_str_mv Gibaja, Alejandro
Alvarado Romero, Juan Carlos
Scheper, Verena
Carles, Liliana
Juiz Gómez, José Manuel
author Gibaja, Alejandro
author_facet Gibaja, Alejandro
Alvarado Romero, Juan Carlos
Scheper, Verena
Carles, Liliana
Juiz Gómez, José Manuel
author_role author
author2 Alvarado Romero, Juan Carlos
Scheper, Verena
Carles, Liliana
Juiz Gómez, José Manuel
author2_role author
author
author
author
dc.subject.none.fl_str_mv Antibiotic toxicity
Antioxidation
Auditory receptor
Cochlear toxicity
Deafness
topic Antibiotic toxicity
Antioxidation
Auditory receptor
Cochlear toxicity
Deafness
description Kanamycin and cisplatin are ototoxic drugs. The mechanisms are incompletely known. With subcutaneous kanamycin (400 mg/kg, 15 days), auditory threshold shifts were detected at days 12–13 at 16 and 32 kHz, extending to 8 and 4 kHz at days 14–15. The outer hair cell (OHC) loss was concentrated past day 12. The maximum cochlear length showing apoptotic cells, tested with TUNEL, was at day 13. At day 15, 1/5 of the apical cochlea contained preserved OHCs. 3-nitrotyrosine (3-NT) immunolabeling, showing oxidative stress, was found in surviving OHCs and in basal and middle portions of the stria vascularis (SV). The antioxidant Gpx1 gene expression was decreased. The immunocytochemistry showed diminished Gpx1 in OHCs. With intraperitoneal cisplatin (16 mg/kg, single injection), no evoked auditory activity was recorded at the end of treatment, at 72 h. The basal third of the cochlea lacked OHCs. Apoptosis occupied the adjacent 1/3, and the apical third contained preserved OHCs. 3-NT immunolabeling was extensive in OHCs and the SV. Gpx1 and Sod1 gene expression was downregulated. Gpx1 immunostaining diminished in middle and basal SV. More OHCs survived cisplatin than kanamycin towards the apex, despite undetectable evoked activity. Differential regulation of antioxidant enzyme levels suggests differences in the antioxidant response for both drugs.
publishDate 2022
dc.date.none.fl_str_mv 2022
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://doi.org/10.3390/antiox11091759
https://hdl.handle.net/10578/33175
url https://doi.org/10.3390/antiox11091759
https://hdl.handle.net/10578/33175
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv SBPLY/17/180501/000544
EXC 2177/1,ID: 390895286
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869425157813043200
score 15,300719

Similares en LA Referencia